The objectives of this proposal are: 1. To develop more efficient cell fusion techniques, particularly ones not requiring the use of virus, in order to facilitate the production of cell hybrids required for the following objectives. 2. To determine the molecular processes associated with the modulation of HPRT specific activity in the available mouse A9/chick hybrids, and in any additional such cells which can be made, in order to clarify mechanisms by which cells regulate gene activity. 3. To utilize hybrids between nonmalignant and malignant cells in order to determine if a specific chromosome or chromosomes of the nonmalignant parent can suppress the malignant characteristics of the cancer cell. 4. To attempt to develop methods for activating inactive genes in mammalian cells. 5. To attempt to determine if the human Y chromosome carries genes for histocompatibility antigens by utilizing a hamster/human hybrid cell line we have made which has retained only the human Y chromosome.